(a) Field of the Invention
This invention relates to novel 1,4-dihydro-4-oxo-3-quinolinecarboxamides, to methods for the preparation thereof, and compositions and methods for the use thereof as antiviral agents.
(b) Information Disclosure Statement
1,4-Dihydro-4-oxo-3-quinolinecarboxylic acids constitute a well-known class of compounds having antibacterial activity. They are, however, essentially devoid of antiviral activity. Representative acids in the prior art are the following:
1,4-Dihydro-1-ethyl-7-(4-pyridinyl)-4-oxo-3quinolinecarboxylic acid [Lesher et al. U.S. Pat. No. 3,753,993, issued August 21, 1973].
1,4-Dihydro-6,8-difluoro-1-ethyl-7-(4-pyridin-yl)-4-oxo-3-quinolinecarboxyl ic acid [Gilligan et al. U.S. Pat. No. 4,636,506, issued Jan. 13, 1987].
1,4-Dihydro-6-fluoro-1-(p-fluorophenyl)-4-oxo-7(1-piperazinyl)-3-quinolinec arboxylic acid [Chu U.S. Pat. No. 4,730,000, issued Mar. 8, 1988].
1,4-Dihydro-4-oxo-3-quinolinecarboxamides which are known in the art include the following: 1,4-Dihydro-1-methyl-4-oxo-3-quinolinecarboxamide [Angelino et al., J. Heterocyclic Chem. 21, 107 (1984)]. No utility is disclosed for the compound.
N-(1-Tetrazolyl)-1,4-dihydro-1-ethyl-7-(4-methyl-1-piperazinyl)-4-oxo-3-qui nolinecarboxamide Allen and Hanburys Ltd. British Patent No. 1,433,774, granted Apr. 28, 1976]. The compounds of the patent are stated to be anti-allergic agents.
Boots Company European Patent Application Publ. No. 172004 (published 2-19-86) contemplates compounds of the formula ##STR2## in which the dotted line between positions 2 and 3 of the quinolone ring represents an optional bond; R is hydrogen or lower alkyl; R.sub.1 is lower alkyl; and R.sub.2, R.sub.3 and R.sub.4, which may be the same or different, are hydrogen, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulphinyl, lower alkylsulphonyl, trifluoromethyl, cyano, fluorinated lower alkoxy, phenyl optionally substituted by one or two substituents selected from lower alkyl, lower alkoxy, lower alkylthio, halo and trifluoromethyl, the group --OAr or the group --S(O).sub.n Ar in which Ar is phenyl optionally substituted by one or two substituents selected from lower alkyl, lower alkoxy, lower alkylthio, halo and trifluoromethyl and n is 0, 1 or 2, or the group --NR.sub.5 R.sub.6 or the N-oxide thereof in which R.sub.5 and R.sub.6, which may be the same or different, are lower alkyl or, together with the nitrogen atom to which they are attached, form a 5 to 7 membered ring optionally containing an additional hetero atom selected from oxygen, nitrogen and sulphur. The compounds reduce blood pressure when administered to hypertensive mammals.
Specific compounds disclosed in the Boots specification include:
7-Fluoro-1-methyl-4-oxo-1,4-dihydroquinoline-3carboxamide (Example 1b)
7-Chloro-1-methyl-4-oxo-1,4-dihydroquinoline-3carboxamide (Example 4)
7-Chloro-1,N-dimethyl-4-oxo-1,4-dihydroquino-line-3-carboxamide (Example 7).